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Prostate diseases affect millions of men every year around the world. Congenital malformations, prosta-

titis (acute, chronic bacterial and chronic abacterial), benign prostatic hyperplasia (BPH), and prostate cancer comprise most of the abnormalities in the gland. However, special attention is given to prostate cancer, as it is a leading cause of morbidity and mortality among men, es-pecially in western countries.

Within the United States, the num-ber of newly diagnosed prostate cancer patients in 2010 was estimated to be 217,730, and the number of deaths esti-mated to be 32,050.1 As with other forms of cancer, prostate cancer is most effec-tively treated when diagnosed early in its progression. Improved diagnostic meth-ods, therefore, are critical to effective treatment and better patient outcome.2

Today the detection of prostate can-cer begins with prostate-specific-anti-gen (PSA) levels and/or digital rectal examination (DRE). If either of these are abnormal, a transrectal ultrasound (TRUS)-guided biopsy is often the next step. Thus, a prostate cancer diagnosis is typically made through TRUS-guided

sextant biopsy and histopathological examination. The false negative rate of TRUS-guided biopsies is estimated to be between 15% and 34%. Prob-lems arise when, despite a high degree of suspicion for cancer (based upon PSA/DRE), a pathological diagnosis cannot be confirmed. In such patients, magnetic resonance imaging (MRI) can help in one of 3 ways that are dis-cussed below.

MRI is accepted as the best imaging modality for displaying anatomical de-tails of the prostate. MRI has typically been incorporated as a staging tool after a diagnosis is made through a transrec-tal biopsy.3 Recently, the authors and others have described a new role for MRI involving detection of suspicious foci and MRI-guided biopsy of these areas. This article reviews the current impact of MRI on choice of therapy and treatment planning.

The selection of therapy is especially important when there is a risk for stage-T3 disease with extraglandular exten-sion (EGE)4 In these cases, MR imaging with an endorectal coil can achieve posi-tive predictive values between 85% and 97% for extracapsular extension (ECE) and seminal vesicle invasion (SVI), re-spectively.5,6 Not surprisingly, it is more accurate in localizing tumors than either TRUS-guided biopsy or digital rectal examination. New multiparametric MRI (Mp-MRI) at 3.0 tesla (T) using the en-dorectal coil offers a much improved examination to detect a tumor, localize it

accurately, and characterize the tissue to correlate with the Gleason biopsy score. With the introduction of new treatment strategies, such as cryotherapy, brachy-therapy, and focused ultrasound, more precise information regarding tumor extent is needed.7-9 MRI offers a new opportunity to patients with negative TRUS-guided biopsies. For example, an MRI evaluation even before the TRUS-guided biopsy could be beneficial, espe-cially for patients at risk for high-grade tumors or tumors in the transitional zone (TZ) or central gland.10 Thus, MRI of the prostate is fulfilling multiple roles in regard to prostate cancer, including im-proving diagnostic accuracy; enabling risk stratification, initial staging, surveil-lance of cancer recurrence and treatment response; characterization of prostatic tissue; and, more recently, guidance of focal therapy or biopsy for diagnosis.11

Prostate anatomyThe prostate resembles an inverted

cone located right under the bladder, lying anterior to the rectum and poste-rior to the pubic bone, postero-laterally surrounded by the neurovascular bundle (NVB). The seminal vesicles are located postero-superiorly to the gland and, to-gether with the NVB, make up the pref-erential paths for tumor spread once the tumor has penetrated the prostatic cap-sule. The gland is divided into 3 zones: the peripheral (PZ), transition (TZ) and central (CZ) zones. The first constitutes most of the glandular tissue within the

Prostate MRI: Update and current roles

Clare Tempany, MD, and Felipe Franco

Dr. Tempany is the Ferenc Jolesz Distinguished Chair of Radiology Research, Professor of Radiology Harvard Medical School, Depart-ment of Radiology, Brigham and Women’s Hospital, Boston, MA; and Mr. Franco is a Medical Student from the University of Sao Paulo, Sao Paulo Brazil.

Reprinted with permission: Applied Radiology 2012, Vol. 41, No. 3, pages 17–22

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organ and is the origin of most tumors of glandular origin (approximately 70%), followed by 20% and 10% in the TZ and CZ, respectively. It is important to point out that the boundaries between the CZ and TZ are difficult to find through imaging; therefore, both are frequently dominated by the central gland (Fig- ures 1 and 2).

For localization purposes, the pros-tate gland is usually arbitrarily divided into the apex, middle gland, and base. This can define the traditional prostatic sextants used for TRUS-guided biopsy and correlation with histology samples.

Current techniquesPrevious reports and experience have

established the feasibility, reliability, and ease of prostate MRI at 1.5T that is being rapidly overshadowed by the shift to 3T high-field MRI scanners. Studies have shown that higher-field scanners using T1-weighted (T1W) and T2-weighted

(T2W) sequences allow for better spatial and temporal resolution with a higher signal-to-noise ratio (SNR). The im-proved SNR has led to the introduction of new sequences, such as diffusion-weighted imaging (DWI) and dynamic contrast-enhanced sequences. More-over, with shorter acquisition times, such powerful magnets, enable Mp-MRI stud-ies of the prostate to be run in only one session without major complications or patient discomfort.

In addition to the use of 3T magnets, another advance in MRI with respect to prostate cancer is the use of an en-dorectal coil with a pelvic coil. This approach has the advantage of increas-ing SNR with fewer artifacts and bet-ter image resolution than MRI without the endorectal coil. On the other hand, it creates discomfort for the patient and deforms the gland. However, one recent study indicated that the combination provides higher accuracy; thus, the use

of the endorectal and pelvic coils is sug-gested for most studies.12 It has been said that a prostate exam at 1.5T with an endorectal coil is equivalent to one at 3.0T without the coil without further improvement or gain from 3.0T. Thus, many groups continue to use the en-dorectal coil and at the same time maxi-mize the advantages of the higher field strength. If the endorectal coil is used, the patient should have IV/IM admin-istration of buscopolamyne or glucagon to decrease the intestinal peristaltic ac-tivity during the examination.

The endorectal coil is lubricated with a topical anesthetic (usually xylo-caine or lidocaine), inserted and inflated with 60 ml to 80 ml of either air or liq-uid perfluorocarbon, which can reduce air associated artifacts (Figure 3). The waiting time after biopsy to perform a scan is controversial. In general, clini-cians advocate waiting about 4 weeks after biopsy with some advocating up to 8 weeks to prevent artifacts from he-matoma or prostatic inflammation. In-terestingly, some studies have pointed out that the artifact may not resolve for months, creating anxiety for the patient during the interval between biopsy and the MRI study waiting for a definitive diagnosis.

MRI sequences for the prostate

T2W MRI is a very well established and essential sequence, compared with other techniques, as it provides an ex-cellent display of the prostate and its substructure anatomy. Focal tumor usually appears as an area of low sig-nal surrounded by the high signal of the normal PZ. It is sometimes chal-lenging to detect carcinoma in the PZ due to several factors that may mimic malignant foci, such as postbiopsy hemorrhage, benign prostatic hyper-trophy, scars, fibromuscular tissue, calcifications, prostatitis, and the ef-fects of radiation treatment. Even more challenging may be the detection of neoplastic tissue in the central gland where nodules appear with mixed sig-nal intensities (Figure 4). If there is a homogeneous lenticular shape with low

FIGURE 1. T2-weighted image showing the PZ (yellow) and central gland (red). Axial view.

FIGURE 2. T2-weighted image in coronal view.

FIGURE 3. T2-weighted sagittal view shows the ideal position of the e-coil.

FIGURE 4.T2-weighted image in axial view. It is hard to distinguish cancerous and non-cancerous tissue, especially in the central gland.

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signal on T2W, a central gland focal cancer should be suspected.

Due to its limitations, T2W alone does not achieve adequate sensitivity and specificity for prostate cancer. High signal areas in T1W overlapping with low-signal areas on T2W are likely to produce artifacts due to postbiopsy hem-orrhage. To avoid this error and enable higher diagnostic accuracy, Mp-MRI techniques are now widely used. DWI, magnetic resonance spectroscopy imag-ing (MRSI), dynamic contrast enhance-ment (DCE) and its postprocessed maps are now part of a state-of-the-art MR imaging set and can increase the detec-tion of significant prostate cancer, mark-edly improving diagnostic capability. In the DCE series, many images are ob-tained at different phases after the bolus of gadolinium has circulated through the prostate. The raw data can demonstrate areas of enhancement and can be used to estimate the presence of focal cancer. However, the raw data can be analyzed in various ways, one of which is in a contrast kinetics software program that models blood flow and tissue reaction to produce individual sets of images in color illustrating different pharmo-ki-netic parameters. The postprocessed val-ues acquired with these new techniques can be validated quantitatively using color maps that are visually clear and through objective metrics, such as appar-ent diffusion coefficient (ADC) maps as well as with parameters from 2 compart-ment pharmacokinetic models, such as ktrans (wash-in) kep (wash-out), maxi-mum slope for wash-in and wash-out, and Ve (extravascular–extracellular vol-ume fraction) (Figure 5). Mp-MRI com-bined with traditional T2W can be used not only to analyze the presence or ab-sence of prostate carcinoma and to plan therapy but also to characterize the histo-logical features of tumors. One study has shown that Mp-MRI is correlated to tis-sue composition for tumors and benign tissue,13 and it can allow for differentia-tion between BPH and prostate cancer in the central gland.14 Mp-MRI can also be used with good accuracy for determining recurrence after local salvage therapy.15

A

C

B

D

FIGURE 5. Color maps of the area suspicious for cancer in Figure 4. (A) Ktrans, (B) kep, and (C) max slope are obtained in same area suspicious for harboring a tumor in the central gland. (D) Interestingly, the same area is not suspicious using Ve modeling.

A B

FIGURE 6. (A) An ADC map in the axial view shows an area suspicious for cancer in the central gland. A T1-weighted image (B) in axial view shows marked enhancement of central gland. These images are from the same patient as those in Figure 4.

A B

FIGURE 7. (A) T2-weighted image in axial view. The patient presents with extracapsular extension, and the tumor is invading the bladder. (B) T2-weighted image in coronal view. Images of the patient are shown in Figure 5.

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An ideal combination of all these se-quences and postprocessed data must still be established, but it will certainly rely on the combination of several differ-ent sequences to reach the highest levels of accuracy in cancer detection and char-acterization.16

DWI MRIFirst described to assess stroke and

ischemia in the brain, diffusion-weighted imaging (DWI) measures the water dif-fusion within tissue. It is well known that neoplasia, due to its local neoangiogen-esis, usually affects the diffusion capacity of water molecules; therefore, this tech-nique can be used in prostate imaging, al-lowing for short acquisition times and no need for IV contrast medium administra-tion.17 DWI sequences are acquired using a range of b values (500, 1000, and 1400) to generate ADC maps. More recently the higher b values—over 1000 —have shown great promise for the detection and characterization of focal tumors. Tu-mors show a lower ADC value than be-nign regions, both in PZ and the central gland (Figure 6). One study has shown that the lower the ADC value, the higher the Gleason score and the more aggres-sive the tumor is—with higher clinical risk—for those tumors in the PZ.18

The addition of an ADC map to T2W images can improve the diagnostic performance of MR imaging in prostate cancer detection,16 helping to distin-guish malignant from benign tissues. Accounting for a finite water exchange rate between cells and their environ-ment may also aid staging accuracy and the ability to monitor response to treat-ment.19 The combination of ADC and T2W can be used to differentiate cell

density both in cancerous and noncan-cerous tissue and, therefore it plays an important role in the estimation of the Gleason score at 3T.20

DCE and pharmacokinetic models—applied color maps

DCE (dynamic contrast-enhanced) imaging was introduced to effectively visualize the pharmacokinetics of gado-linium uptake in tissue as tumors’ angio-genesis differs from that of benign tissue. DCE imaging acquires data on tissue per-fusion characteristics and tumor wash-in and wash-out contrast that are variables which rely on the pathophysiologic prin-ciple that tumors display increased angio-genesis, and, thus, are expected to show early and increased enhancement.

DCE imaging for prostate is evalu-ated by means of the direct raw inter-pretation of T1W images played in cine mode (Figure 6) and from color maps generated from 2 compartment pharma-cokinetic models. The following general kinetic models are usually selected for processing: ktrans, kep, maximum slope for wash-in and wash-out, and Ve (ex-travascular–extracellular volume frac-tion) (Figure 5). The mean peak values of ktrans (forward value transfer constant), kep (reverse reflux rate constant between extracellular space and plasma), time to peak (TTP) and maximum slope (MaxS) are currently the parameters of most

Table 1- Parameters for diagnostic prostate MRI used by our group

Sequence TR/TE Matrix FOV Flip angle Slice thickness

T2WI Coronal 2416/106 512 X 512 100 90 3T2WI Sagittal 2933/98 512 X 512 100 90 3T2WI Axial 2400/100 512 X 512 100 65 3DWI (b values 0-500,0-1000, 0-1400) 2500/80.7 256 X 256 60 90 33D Axial T1WI pre contrast 30 (5 flip) 5.512/2.1 256 X 256 100 30 6Axial FSPGR FST1 precontrast 385/6.59 512 X 512 100 65 33D DCE Axial FSPGR FST1 3.75/1.33 256 X 256 100 15 6 postcontrast (15 flip) Axial FSPGR FST1 postcontrast 385/6.59 512 X 512 100 65 3Axial FSPGR FST1 post (breath hold) 225/3.31 256 X 256 100 75 6

TR/TE=repetition time/echo time (ms), FOV=field of view (mm), Flip angle (degrees), Slice thickness (mm)

FIGURE 9. T2-weighted axial view showing the location of brachytherapy seeds.

FIGURE 8. Needle artifact (arrow) is seen in a T2-weighted image during a biopsy procedure.

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interest. These processed data can be analyzed either visually (by generating color maps) or quantitatively through straight values.

Quantitative measurements reflect some exciting results and can play an even greater role in the future of prostate care. Prostate MRI methods may one day substitute for some of the in vivo as-sessments done today by histology or, perhaps more importantly, guide focal therapy and enable the careful monitor-ing of therapy after delivery. Though the difference in impact is only significant for evaluating the PZ, quantitative dynamic MRI is more accurate than T2W imag-ing for tumor localization of nonpalpable cancer greater than 0.2 cm3. Above this volume, correlation between tumor vol-ume measured on dynamic MRI and that on the specimen is poor.14, 21 With that said, DCE imaging is a proven method to help localize tumors within the prostate.

SpectroscopyMR spectroscopy is another tech-

nique that allows one to noninvasively assess metabolites present in biologi-cal tissue. Given that the use of an MRI body coil alone does not reach sufficient resolution, clinical practice improved once the endorectal coil was introduced, as it provided 3D MRSI of the prostate with increased sensitivity. Currently, the resolution of MRSI with 1.5T scan-ners is a voxel size of approximately 0.3 cm,3 while for 3T, voxels smaller than 0.2 cm3 are feasible. The levels of citrate, choline, and creatine are useful

for the evaluation of prostate cancer, as it is known that tumors have an elevated level of choline and a decreased level of citrate. Though it is important to point out that the graphical analysis of creatine and choline is usually not separable, the ratio (choline + creatine/citrate) can be used for the prediction of malignancy. Several studies have tried to suggest lev-els of these substances as predictors for prostate cancer. In a recent study, Kumar et al showed a good prediction for tumor detection when a cutoff of 1.2 in (citrate/choline+creatine) ratio was used to as-sess the likelihood of malignancy in the PZ. However, there is still no agreement among studies about concentrations of metabolites in diagnosing cancer. This lack of consensus is probably due to dif-ferences in technique for data acquisition and interpretation; indeed, no standard has been reached. Studies have shown specificities of 49% to 88% with accom-panying sensitivities of 63% to 98%, respectively, for MRSI. Unfortunately, most of these good results excluded analysis of the central gland.4 Due to sig-nal overlapping from the PZ, MRSI still does not obtain highly accurate results in the inner regions of the prostate. More-over, a recent multi-institutional pro-spective study demonstrated that MRSI combined with MRI achieves the same levels of accuracy for detecting tumors in the PZ compared to MRI alone.22

Current suggested protocolCurrent state-of-the-art MRI tech-

niques for prostate care are performed

on 3T magnets and are based on the following sequences: T2W fast spin echo in 3 orthogonal orientations; axial unenhanced T1W; and dynamic axial 3-dimensional fast spoiled gradient echo T1W for 90 sec after injection of contrast. These data are then processed by specialized software to yield color maps for the DCE series and ADC maps from generated raw DWI. This protocol has been satisfactorily used for the last 5 years for prostate cancer detection, stag-ing, and assessment of radiation therapy at the Brigham and Women’s Hospital in Boston. Moreover, the protocol has been endorsed by 16 European experts at a recent meeting.23

Staging, localization, and treatment planning

Overall staging is based on whether tumor is organ confined (T1/T2) or beyond the prostatic tissue (T3/T4). SVI (seminal vesicle invasion) and extracap-sular extension (ECE) are important fac-tors for staging disease (Figure 7). For SVI, the accepted criteria are low signal intensity in one or both SV (usually high signal in T2W) or disruption or loss of the normal architecture in the ducts or the glands, whereas the criteria for ECE are tumor extension into the periprostatic fat tissue, focal capsular bulge, irregularity, retraction, and rectoprostatic angle oblit-eration.24 ECE initially occurs most com-monly at the 5 and 7 o’clock locations in the axial plane. Wang et al17 showed that MRI has better accuracy for predicting SVI than clinical variables. Moreover,

FIGURE 10. Patient suspected of harboring a tumor in the left PZ (A and B). Suspicious foci are marked with the T2-weighted sequence dur-ing biopsy (C). Registration methods allow alignment of the diagnostic T2-weighted images. These methods make possible the confirmation of needle placement not only visually but also mathematically.

A B C

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the endorectal MRI has shown the most promising results in detecting SVI with specificity up to 99% and sensitivity up to 80%. For assessing ECE, MRI (T2W) has a reported accuracy of between 50% and 90%.24 The typical workflow for the staging of prostate cancer by MRI is shown on Table 1.

Even though MRI techniques, such as DCE and MRS, cannot detect pre-cancerous lesions, such as prostatic in-traepithelial neoplasia, MRI is useful for predicting a tumor’s grade. Treat-ment choice, including active surveil-lance, relies on MRI to assist in the prediction of a tumor’s behavior; one important aspect of this is the tumor size and prostate volume. For example, MRI is known to be better than TRUS for as-sessing prostate volume, which is very important to know for radiation therapy to optimize outcomes. For instance, pa-tients must be defined as having a pros-tate smaller than 60 cc for them to be deemed suitable for external beam ra-diation therapy or brachytherapy.

The criteria for staging prostate car-cinoma not only involves defining ECE and SVI but it also should concomitantly evaluate pelvic lymph nodes and osseous structures to detect all sites of possible metastases in a single examination.11

ConclusionBased upon the published litera-

ture, we believe that MRI will become a more requested exam for prostate evaluation and will play a more central role in the diagnosis of prostate cancer. It could significantly reduce the de-gree of diagnostic uncertainty that now plagues many clinicians and their pa-tients, provide an excellent “biomarker” for men undergoing active surveillance for nonsignificant disease, and allow for improved selection of treatment for those with significant tumors. Current research includes the development of new MRI sequences for 3T magnets that offer the undervalued benefit of de-creasing patient examination time.

Moreover, research by several groups using interventional techniques (such as biopsy) under MRI guidance (Figure 8)

show improved diagnostic accuracy and allow for novel treatment options, such as targeted therapy with focused ultra-sound, cryotherapy, or laser.25 Anatomi-cal detail, only depicted by MRI, ensures the feasibility of focal treatments, such as external beam radiation, seed placement during brachytherapy, and focal abla-tion by high-intensity focused ultrasound (HIFU) (Figure 9). Moreover, software, such as the open source 3D Slicer (www.slicer.org) with a prostate module called ProstateNav, provides image registration methods and offers guidance to the inter-ventional radiologist, showing details, such as prostate movement and intrapro-cedure deformation, enabling accurate biopsy needle placement (Figure 10).26

Acknowledgments: The authors thank Kimberly Lawson for help in ed-iting, preparing, and overseeing this work, and Darcell McKenzie for admin-istrative assistance.

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10. Ahmed HU, Kirkham A, Arya M, et al. Is it time to consider a role for MRI before prostate biopsy? Nat Rev Clin Oncol. 2009;6:197-206.11. Kelloff GJ, Choyke P, Coffey DS. Challenges in clinical prostate cancer: Role of imaging. AJR Am J Roentgenol. 2009; 192:1455-1470.12. Heijmink SW, Futterer JJ, Hambrock T, et al. Prostate cancer: Body-array versus endorectal coil MR imaging at 3T--comparison of image quality, localization, and staging performance. Radiology. 2007;244:184-195.13. Langer DL, van der Kwast TH, Evans AJ, et al. Prostate tissue composition and MR measure-ments: Investigating the relationships between ADC, T2, K(trans), v(e), and corresponding histo-logic features. Radiology. 2010;255:485-494.14. Oto A, Kayhan A, Jiang Y, et al. Prostate tissue composition and MR measurements: Investigating the relationships between ADC, T2, K(trans) MR imaging. Radiology. 2010;257:715-723.15. Arumainayagam N, Kumaar S, Ahmed HU, et al. Accuracy of multiparametric magnetic reso-nance imaging in detecting recurrent prostate can-cer after radiotherapy. BJU Int. 2010;106:991-997.16. Turkbey B, Pinto PA, Mani H, et al. Prostate cancer: Value of multiparametric MR imaging at 3T for detection--histopathologic correlation. Radiol-ogy. 2010;255:89-99.17. Wang L, Hricak H, Kattan MW, et al. Predic-tion of seminal vesicle invasion in prostate can-cer: Incremental value of adding endorectal MR imaging to the Kattan nomogram. Radiology. 2007;242:182-188.18. Turkbey B, Shah VP, Pang Y, et al. Is appar-ent diffusion coefficient associated with clinical risk scores for prostate cancers that are visible on 3-T MR images? Radiology. 2011;258:488-495.19. Lowry M, Zelhof B, Liney GP, et al. Analysis of prostate DCE-MRI: Comparison of fast exchange limit and fast exchange regimen pharmacokinetic models in the discrimination of malignant from nor-mal tissue. Invest Radiol. 2009;44:577-584.20. Gibbs P, Liney GP, Pickles MD, et al. Correla-tion of ADC and T2 measurements with cell den-sity in prostate cancer at 3.0 Tesla. Invest Radiol. 2009;44:572-576.21. Mullerad M, Hricak H, Kuroiwa K, et al. Com-parison of endorectal magnetic resonance imaging, guided prostate biopsy and digital rectal examina-tion in the preoperative anatomical localization of prostate cancer. J Urol. 2005;174:2158-2163.22. Weinreb JC, Blume JD, Coakley FV, et al. Prostate cancer: Sextant localization at MR imaging and MR spectroscopic imaging before prostatectomy--results of ACRIN prospective multi-institutional clinicopathologic study. Radiol-ogy. 2009; 251:122-133.23. Dickinson L, Ahmed HU, Allen C, et al. Mag-netic resonance imaging for the detection, locali-sation, and characterisation of prostate cancer: Recommendations from a European consensus meeting. Eur Urol. 2011;59:477-494.24. Futterer JJ. MR imaging in local staging of prostate cancer. Eur J Radiol. 2007;63:328-334.25. Tempany C, Straus S, Hata N, Haker S. MR-guided prostate interventions. J Magn Reson Imaging. 2008;27:356-367.26. Tokuda J, Fischer GS, Csoma C, et al. Soft-ware strategy for robotic transperineal prostate therapy in closed-bore MRI. Med Image Comput Comput Assist Interv. 2008;11:701-709.